Background: Early diagnosis is essential in the field of lysosomal storage disorders for the proper management of patients and for starting therapies before irreversible damage occurs, particularly in neurodegenerative conditions. Currently, specific biomarkers for the diagnosis of lysosomal storage disorders are lacking in routine laboratory practice, except for enzymatic tests, which are available only in specialized metabolic centers. Recently, we established a method for measuring and verifying changes in GM1 ganglioside levels in peripheral blood lymphocytes in patients with GM1 gangliosidosis. However, fresh blood is not always available, and using frozen/thawed lymphocytes can lead to inaccurate results.
Methods: We used frozen/thawed fibroblasts obtained from stored biopsies to explore the feasibility of fluorescent imaging and flow-cytometric methods to track changes in storage materials in fibroblasts from patients with three lysosomal neurodegenerative conditions: GM1 gangliosidosis, Sialidosis, and Niemann-Pick type C. We used specific markers for each pathology.
Results And Conclusions: We demonstrated that with our methods, it is possible to clearly distinguish the levels of accumulated metabolites in fibroblasts from affected and unaffected patients for all the three pathologies considered. Our methods proved to be rapid, sensitive, unbiased, and potentially applicable to other LSDs.
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| http://dx.doi.org/10.3390/biomedicines10081962 | DOI Listing |
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A natural history study of pediatric patients with early onset of GM1 gangliosidosis, GM2 gangliosidoses, or gaucher disease type 2 (RETRIEVE).
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Division of Metabolism and Children's Research Center, Reference Center for Inborn Errors of Metabolism, University Children's Hospital of Zurich, University of Zurich, Zurich, Switzerland.
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Differential Tractography: A Biomarker for Neuronal Function in Neurodegenerative Disease.
medRxiv
August 2024
Office of the Clinical Director and Medical Genetics Branch, National Human Genome Research Institute, 10 Center Drive, Bethesda MD USA.
GM1 gangliosidosis is an ultra-rare inherited neurodegenerative lysosomal storage disorder caused by biallelic mutations in the gene. GM1 is uniformly fatal and has no approved therapies, although clinical trials investigating gene therapy as a potential treatment for this condition are underway. Novel outcome measures or biomarkers demonstrating the longitudinal effects of GM1 and potential recovery due to therapeutic intervention are urgently needed to establish efficacy of potential therapeutics.
View Article and Find Full Text PDFQuantitative reliability assessment of brain MRI volumetric measurements in type II GM1 gangliosidosis patients.
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Image Processing and Analysis Core (iPAC), Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, United States.
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Generation of an infantile GM1 gangliosidosis induced pluripotent stem cell line (CHOCi005-A) for disease modeling and therapeutic testing.
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Division of Metabolic Disorders, Children's Hospital of Orange County Specialists, Orange, CA 92868, United States; Department of Pediatrics, University of California-Irvine School of Medicine, Irvine, CA 92697, United States. Electronic address:
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Base editing of the GLB1 gene is therapeutic in GM1 gangliosidosis patient-derived cells.
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Division of Metabolic Disorders, Children's Hospital of Orange County Specialists, Orange, CA 92868, United States; Department of Pediatrics, University of California-Irvine School of Medicine, Irvine, CA 92697, United States. Electronic address:
GM1 gangliosidosis is an autosomal recessive neurodegenerative lysosomal storage disease caused by pathogenic variants in the GLB1 gene, limiting the production of active lysosomal β-galactosidase. Phenotypic heterogeneity is due in part to variant type, location within GLB1, and the amount of residual enzyme activity; in the most severe form, death occurs in infancy. With no FDA approved therapeutics, development of efficacious strategies for the disease is pivotal.
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